Brain Sciences

20 pages, 1104 KiB

Open AccessEditor’s ChoiceArticle

The Optimization of a Natural Language Processing Approach for the Automatic Detection of Alzheimer’s Disease Using GPT Embeddings

by Benjamin S. Runde, Ajit Alapati and Nicolas G. Bazan

Brain Sci. 2024, 14(3), 211; https://doi.org/10.3390/brainsci14030211 - 25 Feb 2024

Cited by 4 | Viewed by 3428

Abstract

The development of noninvasive and cost-effective methods of detecting Alzheimer’s disease (AD) is essential for its early prevention and mitigation. We optimize the detection of AD using natural language processing (NLP) of spontaneous speech through the use of audio enhancement techniques and novel [...] Read more.

The development of noninvasive and cost-effective methods of detecting Alzheimer’s disease (AD) is essential for its early prevention and mitigation. We optimize the detection of AD using natural language processing (NLP) of spontaneous speech through the use of audio enhancement techniques and novel transcription methodologies. Specifically, we utilized Boll Spectral Subtraction to improve audio fidelity and created transcriptions using state-of-the-art AI services—locally-based Wav2Vec and Whisper, alongside cloud-based IBM Cloud and Rev AI—evaluating their performance against traditional manual transcription methods. Support Vector Machine (SVM) classifiers were then trained and tested using GPT-based embeddings of transcriptions. Our findings revealed that AI-based transcriptions largely outperformed traditional manual ones, with Wav2Vec (enhanced audio) achieving the best accuracy and F-1 score (0.99 for both metrics) for locally-based systems and Rev AI (standard audio) performing the best for cloud-based systems (0.96 for both metrics). Furthermore, this study revealed the detrimental effects of interviewer speech on model performance in addition to the minimal effect of audio enhancement. Based on our findings, current AI transcription and NLP technologies are highly effective at accurately detecting AD with available data but struggle to classify probable AD and mild cognitive impairment (MCI), a prodromal stage of AD, due to a lack of training data, laying the groundwork for the future implementation of an automatic AD detection system. Full article

(This article belongs to the Special Issue Deep into the Brain: Artificial Intelligence in Brain Diseases)

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27 pages, 881 KiB

Open AccessEditor’s ChoiceSystematic Review

Novel Approaches for the Treatment of Post-Traumatic Stress Disorder: A Systematic Review of Non-Invasive Brain Stimulation Interventions and Insights from Clinical Trials

by Daniele Saccenti, Leandro Lodi, Andrea Stefano Moro, Simona Scaini, Barbara Forresi, Jacopo Lamanna and Mattia Ferro

Brain Sci. 2024, 14(3), 210; https://doi.org/10.3390/brainsci14030210 - 24 Feb 2024

Cited by 3 | Viewed by 2617

Abstract

First-line treatments for post-traumatic stress disorder (PTSD) encompass a wide range of pharmacotherapies and psychotherapies. However, many patients fail to respond to such interventions, highlighting the need for novel approaches. Due to its ability to modulate cortical activity, non-invasive brain stimulation (NIBS) could [...] Read more.

First-line treatments for post-traumatic stress disorder (PTSD) encompass a wide range of pharmacotherapies and psychotherapies. However, many patients fail to respond to such interventions, highlighting the need for novel approaches. Due to its ability to modulate cortical activity, non-invasive brain stimulation (NIBS) could represent a valuable therapeutic tool. Therefore, the aim of this systematic review is to summarize and discuss the existing evidence on the ameliorative effects of NIBS on PTSD and comorbid anxiety and depressive symptoms. Our goal is also to debate the effectiveness of an integrated approach characterized by the combination of NIBS and psychotherapy. This search was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines in the PubMed, PsycINFO, PsycARTICLES, PSYINDEX, MEDLINE, and ERIC databases. Overall, 31 studies met the eligibility criteria, yielding a total of 26 clinical trials employing transcranial magnetic stimulation (TMS) and 5 making use of transcranial direct-current stimulation (tDCS). From these studies, it emerged that NIBS consistently reduced overall PTSD symptoms’ severity as well as comorbid anxiety and depressive symptoms. Moreover, we speculate that combining NIBS with prolonged exposure or cognitive processing therapy might represent a promising therapeutic approach for consistently ameliorating subjects’ clinical conditions. Full article

(This article belongs to the Special Issue Neuromodulation of Cortical Networks in Neurological and Neuropsychiatric Disorders: Potential Clinical Indications and the Biophysiological Impact of Stimulation)

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17 pages, 71445 KiB

Open AccessEditor’s ChoiceReview

Operative Corridors in Endoscopic Skull Base Tumor Surgery

by A. Karim Ahmed, Nicholas R. Rowan and Debraj Mukherjee

Brain Sci. 2024, 14(3), 207; https://doi.org/10.3390/brainsci14030207 - 23 Feb 2024

Cited by 3 | Viewed by 1470

Abstract

Advances in technology, instrumentation, and reconstruction have paved the way for extended endoscopic approaches to skull base tumors. In the sagittal plane, the endonasal approach may safely access pathologies from the frontal sinus to the craniocervical junction in the sagittal plane, the petrous [...] Read more.

Advances in technology, instrumentation, and reconstruction have paved the way for extended endoscopic approaches to skull base tumors. In the sagittal plane, the endonasal approach may safely access pathologies from the frontal sinus to the craniocervical junction in the sagittal plane, the petrous apex in the coronal plane, and extend posteriorly to the clivus and posterior cranial fossa. This review article describes these modular extended endoscopic approaches, along with crucial anatomic considerations, illustrative cases, and practical operative pearls. Full article

(This article belongs to the Special Issue Advances in Skull Base Tumor Surgery: The Practical Pearls)

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33 pages, 754 KiB

Open AccessEditor’s ChoiceReview

Neuromodulation of Eating Disorders: A Review of Underlying Neural Network Activity and Neuromodulatory Treatments

by Kevin Wu, Yu Tung Lo, Jonathon Cavaleri, Matthew Bergosh, Jennifer Ipe, Robert G. Briggs, Kay B. Jann, Stuart B. Murray, Xenos L. Mason, Charles Y. Liu and Darrin J. Lee

Brain Sci. 2024, 14(3), 200; https://doi.org/10.3390/brainsci14030200 - 22 Feb 2024

Cited by 2 | Viewed by 3245

Abstract

Eating disorders are a group of psychiatric conditions that involve pathological relationships between patients and food. The most prolific of these disorders are anorexia nervosa, bulimia nervosa, and binge eating disorder. The current standard of care involves psychotherapy, pharmacotherapy, and the management of [...] Read more.

Eating disorders are a group of psychiatric conditions that involve pathological relationships between patients and food. The most prolific of these disorders are anorexia nervosa, bulimia nervosa, and binge eating disorder. The current standard of care involves psychotherapy, pharmacotherapy, and the management of comorbid conditions, with nutritional rehabilitation reserved for severe cases of anorexia nervosa. Unfortunately, many patients often fail to respond, leaving a concerning treatment gap between the current and requisite treatments for eating disorders. To better understand the neurobiology underlying these eating disorders, investigations have been undertaken to characterize the activity of various neural networks, primarily those activated during tasks of executive inhibition, reward processing, and self-reference. Various neuromodulatory techniques have been proposed to stimulate these networks with the goal of improving patients’ BMI and mental health. The aim of this review is to compile a comprehensive summarization of the current literature regarding the underlying neural connectivity of anorexia nervosa, bulimia nervosa, and binge eating disorder as well as the numerous neuromodulatory modalities that have been investigated. Importantly, we aimed to summarize the most significant clinical trials to date as well as to provide an updated assessment of the role of deep brain stimulation, summarizing numerous recently published clinical studies that have greatly contributed to the literature. In this review, we found therapeutic evidence for transcranial magnetic stimulation and transcranial direct current stimulation in treating individuals suffering from anorexia nervosa, bulimia nervosa, and binge eating disorder. We also found significant evidence for the role of deep brain stimulation, particularly as an escalatory therapy option for the those who failed standard therapy. Finally, we hope to provide promising directions for future clinical investigations. Full article

(This article belongs to the Section Behavioral Neuroscience)

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20 pages, 10515 KiB

Open AccessEditor’s ChoiceArticle

A Novel EEG-Based Assessment of Distraction in Simulated Driving under Different Road and Traffic Conditions

by Vincenzo Ronca, Francois Brambati, Linda Napoletano, Cyril Marx, Sandra Trösterer, Alessia Vozzi, Pietro Aricò, Andrea Giorgi, Rossella Capotorto, Gianluca Borghini, Fabio Babiloni and Gianluca Di Flumeri

Brain Sci. 2024, 14(3), 193; https://doi.org/10.3390/brainsci14030193 - 21 Feb 2024

Cited by 5 | Viewed by 1655

Abstract

The drivers’ distraction plays a crucial role in road safety as it is one of the main impacting causes of road accidents. The phenomenon of distraction encompasses both psychological and environmental factors and, therefore, addressing the complex interplay contributing to human distraction in [...] Read more.

The drivers’ distraction plays a crucial role in road safety as it is one of the main impacting causes of road accidents. The phenomenon of distraction encompasses both psychological and environmental factors and, therefore, addressing the complex interplay contributing to human distraction in automotive is crucial for developing technologies and interventions for improving road safety. In scientific literature, different works were proposed for the distraction characterization in automotive, but there is still the lack of a univocal measure to assess the degree of distraction, nor a gold-standard tool that allows to “detect” eventual events, road traffic, and additional driving tasks that might contribute to the drivers’ distraction. Therefore, the present study aimed at developing an EEG-based “Distraction index” obtained by the combination of the driver’s mental workload and attention neurometrics and investigating and validating its reliability by analyzing together subjective and behavioral measures. A total of 25 licensed drivers were involved in this study, where they had to drive in two different scenarios, i.e., City and Highway, while different secondary tasks were alternatively proposed in addition to the main one to modulate the driver’s attentional demand. The statistical analysis demonstrated the reliability of the proposed EEG-based distraction index in identifying the drivers’ distraction when driving along different roads and traffic conditions (all p < 0.001). More importantly, the proposed index was demonstrated to be reliable in identifying which are the most impacting additional driving tasks on the drivers’ distraction (all p < 0.01). Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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20 pages, 823 KiB

Open AccessEditor’s ChoiceSystematic Review

Effects and Mechanisms of Exercise on Brain-Derived Neurotrophic Factor (BDNF) Levels and Clinical Outcomes in People with Parkinson’s Disease: A Systematic Review and Meta-Analysis

by Daan G. M. Kaagman, Erwin E. H. van Wegen, Natalie Cignetti, Emily Rothermel, Tim Vanbellingen and Mark A. Hirsch

Brain Sci. 2024, 14(3), 194; https://doi.org/10.3390/brainsci14030194 - 21 Feb 2024

Cited by 6 | Viewed by 4611

Abstract

Introduction: Exercise therapy may increase brain-derived neurotrophic factor (BDNF) levels and improve clinical outcomes in people living with Parkinson’s disease (PD). This systematic review was performed to investigate the effect of exercise therapy on BDNF levels and clinical outcomes in human PD and [...] Read more.

Introduction: Exercise therapy may increase brain-derived neurotrophic factor (BDNF) levels and improve clinical outcomes in people living with Parkinson’s disease (PD). This systematic review was performed to investigate the effect of exercise therapy on BDNF levels and clinical outcomes in human PD and to discuss mechanisms proposed by authors. Method: A search on the literature was performed on PubMed up to December 2023 using the following key words: Parkinson’s disease AND exercise, exercise therapy, neurological rehabilitation AND brain-derived neurotrophic factor, brain-derived neurotrophic factor/blood, brain-derived neurotrophic factor/cerebrospinal fluid AND randomized clinical trial, intervention study. Only randomized clinical trials comparing an exercise intervention to treatment as usual, usual care (UC), sham intervention, or no intervention were included. Results: A meta-analysis of BDNF outcomes with pooled data from five trials (N = 216 participants) resulted in a significant standardized mean difference (SMD) of 1.20 [95% CI 0.53 to 1.87; Z = 3.52, p = 0.0004, I² = 77%], favoring exercise using motorized treadmill, Speedflex machine, rowing machine, and non-specified exercise. Significant improvements were found in Unified Parkinson’s Disease Rating Scale (UPDRS), UPDRS-III, 6 Minute Walk Test (6MWT), and Berg Balance Scale (BBS). Methodological quality of trials was categorized as “good” in three trials, “fair” in one trial, and “poor” in one trial. Conclusion: Key results of this systematic review are that exercise therapy is effective in raising serum BDNF levels and seems effective in alleviating PD motor symptoms. Exercise therapy confers neuroplastic effects on Parkinson brain, mediated, in part, by BDNF. Full article

(This article belongs to the Special Issue Biomarkers Identification for Neurological Diseases and Neurorehabilitation)

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11 pages, 1741 KiB

Open AccessEditor’s ChoiceArticle

Changes in Structural Neural Networks in the Recovery Process of Motor Paralysis after Stroke

by Ikuo Kimura, Atsushi Senoo and Masahiro Abo

Brain Sci. 2024, 14(3), 197; https://doi.org/10.3390/brainsci14030197 - 21 Feb 2024

Cited by 3 | Viewed by 1516

Abstract

In recent years, neurorehabilitation has been actively used to treat motor paralysis after stroke. However, the impacts of rehabilitation on neural networks in the brain remain largely unknown. Therefore, we investigated changes in structural neural networks after rehabilitation therapy in patients who received [...] Read more.

In recent years, neurorehabilitation has been actively used to treat motor paralysis after stroke. However, the impacts of rehabilitation on neural networks in the brain remain largely unknown. Therefore, we investigated changes in structural neural networks after rehabilitation therapy in patients who received a combination of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) and intensive occupational therapy (intensive-OT) as neurorehabilitation. Fugl-Meyer assessment (FMA) for upper extremity (FMA-UE) and Action Research Arm Test (ARAT), both of which reflected upper limb motor function, were conducted before and after rehabilitation therapy. At the same time, diffusion tensor imaging (DTI) and three-dimensional T1-weighted imaging (3D T1WI) were performed. After analyzing the structural connectome based on DTI data, measures related to connectivity in neural networks were calculated using graph theory. Rehabilitation therapy prompted a significant increase in connectivity with the isthmus of the cingulate gyrus in the ipsilesional hemisphere (p < 0.05) in patients with left-sided paralysis, as well as a significant decrease in connectivity with the ipsilesional postcentral gyrus (p < 0.05). These results indicate that LF-rTMS combined with intensive-OT may facilitate motor function recovery by enhancing the functional roles of networks in motor-related areas of the ipsilesional cerebral hemisphere. Full article

(This article belongs to the Special Issue Clinical Application of Neuroimaging in Cerebral Vascular Diseases)

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Graphical abstract

14 pages, 283 KiB

Open AccessEditor’s ChoiceReview

Revealing the Complexity of Fatigue: A Review of the Persistent Challenges and Promises of Artificial Intelligence

by Thorsten Rudroff

Brain Sci. 2024, 14(2), 186; https://doi.org/10.3390/brainsci14020186 - 19 Feb 2024

Cited by 3 | Viewed by 2935

Abstract

Part I reviews persistent challenges obstructing progress in understanding complex fatigue’s biology. Difficulties quantifying subjective symptoms, mapping multi-factorial mechanisms, accounting for individual variation, enabling invasive sensing, overcoming research/funding insularity, and more are discussed. Part II explores how emerging artificial intelligence and machine and [...] Read more.

Part I reviews persistent challenges obstructing progress in understanding complex fatigue’s biology. Difficulties quantifying subjective symptoms, mapping multi-factorial mechanisms, accounting for individual variation, enabling invasive sensing, overcoming research/funding insularity, and more are discussed. Part II explores how emerging artificial intelligence and machine and deep learning techniques can help address limitations through pattern recognition of complex physiological signatures as more objective biomarkers, predictive modeling to capture individual differences, consolidation of disjointed findings via data mining, and simulation to explore interventions. Conversational agents like Claude and ChatGPT also have potential to accelerate human fatigue research, but they currently lack capacities for robust autonomous contributions. Envisioned is an innovation timeline where synergistic application of enhanced neuroimaging, biosensors, closed-loop systems, and other advances combined with AI analytics could catalyze transformative progress in elucidating fatigue neural circuitry and treating associated conditions over the coming decades. Full article

(This article belongs to the Special Issue The Use of Robotics and Artificial Intelligence in Neurorehabilitation: From Diagnosis to Treatment)

16 pages, 1144 KiB

Open AccessEditor’s ChoiceReview

Amyotrophic Lateral Sclerosis in Long-COVID Scenario and the Therapeutic Potential of the Purinergic System in Neuromodulation

by Júlia Leão Batista Simões, Samantha Webler Eichler, Maria Luíza Raitz Siqueira, Geórgia de Carvalho Braga and Margarete Dulce Bagatini

Brain Sci. 2024, 14(2), 180; https://doi.org/10.3390/brainsci14020180 - 16 Feb 2024

Viewed by 3311

Abstract

Amyotrophic lateral sclerosis (ALS) involves the degeneration of motor neurons and debilitating and possibly fatal symptoms. The COVID-19 pandemic directly affected the quality of life of this group, and the SARS-CoV-2 infection accelerated the present neuroinflammatory process. Furthermore, studies indicate that the infection [...] Read more.

Amyotrophic lateral sclerosis (ALS) involves the degeneration of motor neurons and debilitating and possibly fatal symptoms. The COVID-19 pandemic directly affected the quality of life of this group, and the SARS-CoV-2 infection accelerated the present neuroinflammatory process. Furthermore, studies indicate that the infection may have led to the development of the pathology. Thus, the scenario after this pandemic presents “long-lasting COVID” as a disease that affects people who have been infected. From this perspective, studying the pathophysiology behind ALS associated with SARS-CoV-2 infection and possible supporting therapies becomes necessary when we understand the impact on the quality of life of these patients. Thus, the purinergic system was trained to demonstrate how its modulation can add to the treatment, reduce disease progression, and result in better prognoses. From our studies, we highlight the P2X7, P2X4, and A2AR receptors and how their activity can directly influence the ALS pathway. Full article

(This article belongs to the Special Issue Neuropharmacology and Neuroinflammation)

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15 pages, 1904 KiB

Open AccessEditor’s ChoiceReview

An Overview of UBTF Neuroregression Syndrome

by Anneliesse A. Braden, Jianfeng Xiao, Roderick Hori, Chester Brown and Mohammad Moshahid Khan

Brain Sci. 2024, 14(2), 179; https://doi.org/10.3390/brainsci14020179 - 15 Feb 2024

Cited by 1 | Viewed by 2808

Abstract

Recently, a recurrent de novo dominant mutation in UBTF (c.628G>A, p.Glu210Lys; UBTF E210K) was identified as the cause of a neurological disorder which has been named UBTF Neuroregression Syndrome (UNS), or Childhood-Onset Neurodegeneration with Brain Atrophy (CONDBA). To date, only 17 cases have [...] Read more.

Recently, a recurrent de novo dominant mutation in UBTF (c.628G>A, p.Glu210Lys; UBTF E210K) was identified as the cause of a neurological disorder which has been named UBTF Neuroregression Syndrome (UNS), or Childhood-Onset Neurodegeneration with Brain Atrophy (CONDBA). To date, only 17 cases have been reported worldwide. The molecular etiology is a pathogenic variant, E210K, within the HMG-box 2 of Upstream Binding Transcription Factor (UBTF). UBTF, a nucleolar protein, plays an important role in ribosomal RNA (rRNA) synthesis, nucleolar integrity, and cell survival. This variant causes unstable preinitiation complexes to form, resulting in altered rDNA chromatin structures, rRNA dysregulation, DNA damage, and ultimately, neurodegeneration. Defining clinical characteristics of the disorder include but are not limited to developmental regression beginning at approximately three years of age, progressive motor dysfunction, declining cognition, ambulatory loss, and behavioral problems. Histological and neuroimaging abnormalities include cortical atrophy, white matter deficits, and enlarged ventricles. Herein, we present a detailed overview of all published cases as well as the functional roles of UBTF to better understand the pathophysiology. Bringing undiagnosed cases to the attention of clinicians and researchers by making them aware of the clinical features will improve research and support the development of therapeutic interventions. Full article

(This article belongs to the Special Issue Neuroinflammation in Neuropsychiatric Disorders)

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15 pages, 2625 KiB

Open AccessEditor’s ChoiceArticle

Exploring the Acquisition of Social Communication Skills in Children with Autism: Preliminary Findings from Applied Behavior Analysis (ABA), Parent Training, and Video Modeling

by Daniela Bordini, Ana Cláudia Moya, Graccielle Rodrigues da Cunha Asevedo, Cristiane Silvestre Paula, Décio Brunoni, Helena Brentani, Sheila Cavalcante Caetano, Jair de Jesus Mari and Leila Bagaiolo

Brain Sci. 2024, 14(2), 172; https://doi.org/10.3390/brainsci14020172 - 9 Feb 2024

Cited by 1 | Viewed by 5011

Abstract

Social communication skills, especially eye contact and joint attention, are frequently impaired in autism spectrum disorder (ASD) and predict functional outcomes. Applied behavior analysis is one of the most common evidence-based treatments for ASD, but it is not accessible to most families in [...] Read more.

Social communication skills, especially eye contact and joint attention, are frequently impaired in autism spectrum disorder (ASD) and predict functional outcomes. Applied behavior analysis is one of the most common evidence-based treatments for ASD, but it is not accessible to most families in low- and middle-income countries (LMICs) as it is an expensive and intensive treatment and needs to be delivered by highly specialized professionals. Parental training has emerged as an effective alternative. This is an exploratory study to assess a parental intervention group via video modeling to acquire eye contact and joint attention. Four graded measures of eye contact and joint attention (full physical prompt, partial physical prompt, gestural prompt, and independent) were assessed in 34 children with ASD and intellectual disability (ID). There was a progressive reduction in the level of prompting required over time to acquire eye contact and joint attention, as well as a positive correlation between the time of exposure to the intervention and the acquisition of abilities. This kind of parent training using video modeling to teach eye contact and joint attention skills to children with ASD and ID is a low-cost intervention that can be applied in low-resource settings. Full article

(This article belongs to the Special Issue Autism Spectrum Disorders (ASD) in Low- and Middle-Income Countries (LMICs) and among Immigrants and Minority Groups in High-Income Countries (HICs))

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24 pages, 2837 KiB

Open AccessEditor’s ChoiceReview

Social Brain Perspectives on the Social and Evolutionary Neuroscience of Human Language

by Nathan Oesch

Brain Sci. 2024, 14(2), 166; https://doi.org/10.3390/brainsci14020166 - 7 Feb 2024

Cited by 3 | Viewed by 3831

Abstract

Human language and social cognition are two key disciplines that have traditionally been studied as separate domains. Nonetheless, an emerging view suggests an alternative perspective. Drawing on the theoretical underpinnings of the social brain hypothesis (thesis of the evolution of brain size and [...] Read more.

Human language and social cognition are two key disciplines that have traditionally been studied as separate domains. Nonetheless, an emerging view suggests an alternative perspective. Drawing on the theoretical underpinnings of the social brain hypothesis (thesis of the evolution of brain size and intelligence), the social complexity hypothesis (thesis of the evolution of communication), and empirical research from comparative animal behavior, human social behavior, language acquisition in children, social cognitive neuroscience, and the cognitive neuroscience of language, it is argued that social cognition and language are two significantly interconnected capacities of the human species. Here, evidence in support of this view reviews (1) recent developmental studies on language learning in infants and young children, pointing to the important crucial benefits associated with social stimulation for youngsters, including the quality and quantity of incoming linguistic information, dyadic infant/child-to-parent non-verbal and verbal interactions, and other important social cues integral for facilitating language learning and social bonding; (2) studies of the adult human brain, suggesting a high degree of specialization for sociolinguistic information processing, memory retrieval, and comprehension, suggesting that the function of these neural areas may connect social cognition with language and social bonding; (3) developmental deficits in language and social cognition, including autism spectrum disorder (ASD), illustrating a unique developmental profile, further linking language, social cognition, and social bonding; and (4) neural biomarkers that may help to identify early developmental disorders of language and social cognition. In effect, the social brain and social complexity hypotheses may jointly help to describe how neurotypical children and adults acquire language, why autistic children and adults exhibit simultaneous deficits in language and social cognition, and why nonhuman primates and other organisms with significant computational capacities cannot learn language. But perhaps most critically, the following article argues that this and related research will allow scientists to generate a holistic profile and deeper understanding of the healthy adult social brain while developing more innovative and effective diagnoses, prognoses, and treatments for maladies and deficits also associated with the social brain. Full article

(This article belongs to the Special Issue Neurodevelopmental Disorders and Early Language Acquisition)

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21 pages, 926 KiB

Open AccessEditor’s ChoiceReview

The Diverse Roles of Reactive Astrocytes in the Pathogenesis of Amyotrophic Lateral Sclerosis

by Kangqin Yang, Yang Liu and Min Zhang

Brain Sci. 2024, 14(2), 158; https://doi.org/10.3390/brainsci14020158 - 4 Feb 2024

Cited by 6 | Viewed by 4178

Abstract

Astrocytes displaying reactive phenotypes are characterized by their ability to remodel morphologically, molecularly, and functionally in response to pathological stimuli. This process results in the loss of their typical astrocyte functions and the acquisition of neurotoxic or neuroprotective roles. A growing body of [...] Read more.

Astrocytes displaying reactive phenotypes are characterized by their ability to remodel morphologically, molecularly, and functionally in response to pathological stimuli. This process results in the loss of their typical astrocyte functions and the acquisition of neurotoxic or neuroprotective roles. A growing body of research indicates that these reactive astrocytes play a pivotal role in the pathogenesis of amyotrophic lateral sclerosis (ALS), involving calcium homeostasis imbalance, mitochondrial dysfunction, abnormal lipid and lactate metabolism, glutamate excitotoxicity, etc. This review summarizes the characteristics of reactive astrocytes, their role in the pathogenesis of ALS, and recent advancements in astrocyte-targeting strategies. Full article

(This article belongs to the Special Issue Advances in Neuroinflammation)

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14 pages, 466 KiB

Open AccessEditor’s ChoiceArticle

Internet Gaming Disorder in Children and Adolescents with Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder

by Valerio Simonelli, Antonio Narzisi, Gianluca Sesso, Andrea Salvati, Annarita Milone, Valentina Viglione, Greta Tolomei, Gabriele Masi and Stefano Berloffa

Brain Sci. 2024, 14(2), 154; https://doi.org/10.3390/brainsci14020154 - 2 Feb 2024

Viewed by 3055

Abstract

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have been related to an increased risk for behavioral addictions including online gaming. However, the relationship between these two conditions and Internet gaming disorder (IGD) is still debated. The aim of this study [...] Read more.

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have been related to an increased risk for behavioral addictions including online gaming. However, the relationship between these two conditions and Internet gaming disorder (IGD) is still debated. The aim of this study is to address this topic by exploring the prevalence of IGD in a consecutive sample of ASD youth and ADHD youth, compared with a normal control group, and by assessing selected psychopathological and neuropsychological features in ASD and ADHD patients with and without IGD. This study included 77 ASD patients (67 males, mean age 13.58 ± 2.75 years), 94 ADHD patients (79 males, mean age 11.46 ± 2.47 years), and 147 normal controls (NC) (mean age 13.9 ± 3.0 years, 114 males) that received structured measures for IGD (IAT, IGDS9-SF, and UADI). In the ADHD group, 72.34% of the sample were above the IGD cut-off, compared with 45.45% in the ASD group and 9.5% in the NC group. ASD patients with IGD presented with greater severity and more severe attention problems, with no difference in the ASD core symptoms between patients with and without IGD. In the comparison between the ASD and ADHD groups according to the presence of IGD, ASD patients with IGD were the most severe group according to the CGI (Clinical Global Impression) scale. The follow-up, conducted on 45 patients affected by ASD, showed an improvement in CGI and CGAS (Children’s Global Assessment Scale) scores, but not in the IGD symptoms. These findings could place the diagnosis of ASD as a negative prognostic factor in the follow-up of aspects of video game addiction compared with ADHD. Full article

(This article belongs to the Special Issue Psychiatry and Addiction: A Multi-Faceted Issue)

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18 pages, 778 KiB

Open AccessEditor’s ChoiceReview

Recalibrating the Why and Whom of Animal Models in Parkinson Disease: A Clinician’s Perspective

by Andrea Sturchio, Emily M. Rocha, Marcelo A. Kauffman, Luca Marsili, Abhimanyu Mahajan, Ameya A. Saraf, Joaquin A. Vizcarra, Ziyuan Guo and Alberto J. Espay

Brain Sci. 2024, 14(2), 151; https://doi.org/10.3390/brainsci14020151 - 31 Jan 2024

Cited by 2 | Viewed by 2603

Abstract

Animal models have been used to gain pathophysiologic insights into Parkinson’s disease (PD) and aid in the translational efforts of interventions with therapeutic potential in human clinical trials. However, no disease-modifying therapy for PD has successfully emerged from model predictions. These translational disappointments [...] Read more.

Animal models have been used to gain pathophysiologic insights into Parkinson’s disease (PD) and aid in the translational efforts of interventions with therapeutic potential in human clinical trials. However, no disease-modifying therapy for PD has successfully emerged from model predictions. These translational disappointments warrant a reappraisal of the types of preclinical questions asked of animal models. Besides the limitations of experimental designs, the one-size convergence and oversimplification yielded by a model cannot recapitulate the molecular diversity within and between PD patients. Here, we compare the strengths and pitfalls of different models, review the discrepancies between animal and human data on similar pathologic and molecular mechanisms, assess the potential of organoids as novel modeling tools, and evaluate the types of questions for which models can guide and misguide. We propose that animal models may be of greatest utility in the evaluation of molecular mechanisms, neural pathways, drug toxicity, and safety but can be unreliable or misleading when used to generate pathophysiologic hypotheses or predict therapeutic efficacy for compounds with potential neuroprotective effects in humans. To enhance the translational disease-modification potential, the modeling must reflect the biology not of a diseased population but of subtypes of diseased humans to distinguish What data are relevant and to Whom. Full article

(This article belongs to the Special Issue New Challenges and Future Perspectives in Parkinson’s Disease and Motor Disorders)

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20 pages, 8080 KiB

Open AccessEditor’s ChoiceArticle

Mental Workload Classification and Tasks Detection in Multitasking: Deep Learning Insights from EEG Study

by Miloš Pušica, Aneta Kartali, Luka Bojović, Ivan Gligorijević, Jelena Jovanović, Maria Chiara Leva and Bogdan Mijović

Brain Sci. 2024, 14(2), 149; https://doi.org/10.3390/brainsci14020149 - 31 Jan 2024

Cited by 5 | Viewed by 3754

Abstract

While the term task load (TL) refers to external task demands, the amount of work, or the number of tasks to be performed, mental workload (MWL) refers to the individual’s effort, mental capacity, or cognitive resources utilized while performing a task. MWL in [...] Read more.

While the term task load (TL) refers to external task demands, the amount of work, or the number of tasks to be performed, mental workload (MWL) refers to the individual’s effort, mental capacity, or cognitive resources utilized while performing a task. MWL in multitasking scenarios is often closely linked with the quantity of tasks a person is handling within a given timeframe. In this study, we challenge this hypothesis from the perspective of electroencephalography (EEG) using a deep learning approach. We conducted an EEG experiment with 50 participants performing NASA Multi-Attribute Task Battery II (MATB-II) under 4 different task load levels. We designed a convolutional neural network (CNN) to help with two distinct classification tasks. In one setting, the CNN was used to classify EEG segments based on their task load level. In another setting, the same CNN architecture was trained again to detect the presence of individual MATB-II subtasks. Results show that, while the model successfully learns to detect whether a particular subtask is active in a given segment (i.e., to differentiate between different subtasks-related EEG patterns), it struggles to differentiate between the two highest levels of task load (i.e., to distinguish MWL-related EEG patterns). We speculate that the challenge comes from two factors: first, the experiment was designed in a way that these two highest levels differed only in the quantity of work within a given timeframe; and second, the participants’ effective adaptation to increased task demands, as evidenced by low error rates. Consequently, this indicates that under such conditions in multitasking, EEG may not reflect distinct enough patterns to differentiate higher levels of task load. Full article

(This article belongs to the Special Issue Emerging Topics in Brain-Computer Interface)

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23 pages, 1881 KiB

Open AccessEditor’s ChoiceArticle

Developmental Dyslexia: Insights from EEG-Based Findings and Molecular Signatures—A Pilot Study

by Daniela Theodoridou, Christos-Orestis Tsiantis, Angeliki-Maria Vlaikou, Vasiliki Chondrou, Victoria Zakopoulou, Pavlos Christodoulides, Emmanouil D. Oikonomou, Katerina D. Tzimourta, Charilaos Kostoulas, Alexandros T. Tzallas, Konstantinos I. Tsamis, Dimitrios Peschos, Argyro Sgourou, Michaela D. Filiou and Maria Syrrou

Brain Sci. 2024, 14(2), 139; https://doi.org/10.3390/brainsci14020139 - 28 Jan 2024

Viewed by 3070

Abstract

Developmental dyslexia (DD) is a learning disorder. Although risk genes have been identified, environmental factors, and particularly stress arising from constant difficulties, have been associated with the occurrence of DD by affecting brain plasticity and function, especially during critical neurodevelopmental stages. In this [...] Read more.

Developmental dyslexia (DD) is a learning disorder. Although risk genes have been identified, environmental factors, and particularly stress arising from constant difficulties, have been associated with the occurrence of DD by affecting brain plasticity and function, especially during critical neurodevelopmental stages. In this work, electroencephalogram (EEG) findings were coupled with the genetic and epigenetic molecular signatures of individuals with DD and matched controls. Specifically, we investigated the genetic and epigenetic correlates of key stress-associated genes (NR3C1, NR3C2, FKBP5, GILZ, SLC6A4) with psychological characteristics (depression, anxiety, and stress) often included in DD diagnostic criteria, as well as with brain EEG findings. We paired the observed brain rhythms with the expression levels of stress-related genes, investigated the epigenetic profile of the stress regulator glucocorticoid receptor (GR) and correlated such indices with demographic findings. This study presents a new interdisciplinary approach and findings that support the idea that stress, attributed to the demands of the school environment, may act as a contributing factor in the occurrence of the DD phenotype. Full article

(This article belongs to the Special Issue Neurodevelopmental Disorders and Early Language Acquisition)

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17 pages, 4249 KiB

Open AccessEditor’s ChoiceArticle

Nanoencapsulated Curcumin: Enhanced Efficacy in Reversing Memory Loss in An Alzheimer Disease Model

by Anne Suély Pinto Savall, Jhuly Dorneles de Mello, Eduarda Monteiro Fidelis, Antonio Alvenir Comis-Neto, Maria Regina Nepomuceno, Camila de Oliveira Pacheco, Sandra Elisa Haas and Simone Pinton

Brain Sci. 2024, 14(2), 130; https://doi.org/10.3390/brainsci14020130 - 26 Jan 2024

Cited by 3 | Viewed by 1816

Abstract

Investigating new drugs or formulations that target Alzheimer disease (AD) is critical for advancing therapeutic interventions. Therefore, this study aimed to assess the effectiveness of nanoencapsulated curcumin (NC Curc) in alleviating memory impairment, oxidative stress, and neuroinflammation in a validated AD model. Male [...] Read more.

Investigating new drugs or formulations that target Alzheimer disease (AD) is critical for advancing therapeutic interventions. Therefore, this study aimed to assess the effectiveness of nanoencapsulated curcumin (NC Curc) in alleviating memory impairment, oxidative stress, and neuroinflammation in a validated AD model. Male Wistar rats were given bilateral intracerebroventricular injections of either saline or streptozotocin (STZ) (3 mg/3 µL/site) to establish the AD model (day 0). On day 22, daily oral administrations of curcumin (6 mg/kg), NC Curc (6 mg/kg), or a vehicle (unloaded NC) were initiated and continued for 14 days. NC Curc significantly reversed memory deficits in object recognition and inhibitory avoidance tests induced by STZ. Both formulations of curcumin attenuated elevated acetylcholinesterase activity caused by STZ. Importantly, NC Curc alone effectively mitigated STZ-induced oxidative stress. Additionally, NC Curc treatment normalized GFAP levels, suggesting a potential reduction in neuroinflammation in STZ-treated rats. Our findings indicate that NC Curc improves memory in an AD rat model, highlighting its enhanced therapeutic effects compared to unencapsulated curcumin. This research significantly contributes to understanding the therapeutic and neurorestorative potential of NC Curc in AD, particularly in reversing pathophysiological changes. Full article

(This article belongs to the Special Issue New Insights into Neuropharmacology)

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50 pages, 2491 KiB

Open AccessEditor’s ChoiceReview

Short-Term Effect of Auditory Stimulation on Neural Activities: A Scoping Review of Longitudinal Electroencephalography and Magnetoencephalography Studies

by Kanon Kobayashi, Yasushi Shiba, Shiori Honda, Shinichiro Nakajima, Shinya Fujii, Masaru Mimura and Yoshihiro Noda

Brain Sci. 2024, 14(2), 131; https://doi.org/10.3390/brainsci14020131 - 26 Jan 2024

Cited by 2 | Viewed by 3393

Abstract

Explored through EEG/MEG, auditory stimuli function as a suitable research probe to reveal various neural activities, including event-related potentials, brain oscillations and functional connectivity. Accumulating evidence in this field stems from studies investigating neuroplasticity induced by long-term auditory training, specifically cross-sectional studies comparing [...] Read more.

Explored through EEG/MEG, auditory stimuli function as a suitable research probe to reveal various neural activities, including event-related potentials, brain oscillations and functional connectivity. Accumulating evidence in this field stems from studies investigating neuroplasticity induced by long-term auditory training, specifically cross-sectional studies comparing musicians and non-musicians as well as longitudinal studies with musicians. In contrast, studies that address the neural effects of short-term interventions whose duration lasts from minutes to hours are only beginning to be featured. Over the past decade, an increasing body of evidence has shown that short-term auditory interventions evoke rapid changes in neural activities, and oscillatory fluctuations can be observed even in the prestimulus period. In this scoping review, we divided the extracted neurophysiological studies into three groups to discuss neural activities with short-term auditory interventions: the pre-stimulus period, during stimulation, and a comparison of before and after stimulation. We show that oscillatory activities vary depending on the context of the stimuli and are greatly affected by the interplay of bottom-up and top-down modulational mechanisms, including attention. We conclude that the observed rapid changes in neural activitiesin the auditory cortex and the higher-order cognitive part of the brain are causally attributed to short-term auditory interventions. Full article

(This article belongs to the Section Neuropsychology)

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21 pages, 1541 KiB

Open AccessEditor’s ChoiceReview

The Impact of Inotropes and Vasopressors on Cerebral Oxygenation in Patients with Traumatic Brain Injury and Subarachnoid Hemorrhage: A Narrative Review

by Michele Salvagno, Federico Geraldini, Giacomo Coppalini, Chiara Robba, Elisa Gouvea Bogossian, Filippo Annoni, Eva Vitali, Elda Diletta Sterchele, Costantino Balestra and Fabio Silvio Taccone

Brain Sci. 2024, 14(2), 117; https://doi.org/10.3390/brainsci14020117 - 24 Jan 2024

Cited by 1 | Viewed by 3891

Abstract

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are critical neurological conditions that necessitate specialized care in the Intensive Care Unit (ICU). Managing cerebral perfusion pressure (CPP) and mean arterial pressure (MAP) is of primary importance in these patients. To maintain targeted MAP [...] Read more.

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are critical neurological conditions that necessitate specialized care in the Intensive Care Unit (ICU). Managing cerebral perfusion pressure (CPP) and mean arterial pressure (MAP) is of primary importance in these patients. To maintain targeted MAP and CPP, vasopressors and/or inotropes are commonly used. However, their effects on cerebral oxygenation are not fully understood. The aim of this review is to provide an up-to date review regarding the current uses and pathophysiological issues related to the use of vasopressors and inotropes in TBI and SAH patients. According to our findings, despite achieving similar hemodynamic parameters and CPP, the effects of various vasopressors and inotropes on cerebral oxygenation, local CBF and metabolism are heterogeneous. Therefore, a more accurate understanding of the cerebral activity of these medications is crucial for optimizing patient management in the ICU setting. Full article

(This article belongs to the Section Molecular and Cellular Neuroscience)

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41 pages, 911 KiB

Open AccessEditor’s ChoiceReview

Brain Functional Correlates of Resting Hypnosis and Hypnotizability: A Review

by Vilfredo De Pascalis

Brain Sci. 2024, 14(2), 115; https://doi.org/10.3390/brainsci14020115 - 24 Jan 2024

Cited by 5 | Viewed by 4387

Abstract

This comprehensive review delves into the cognitive neuroscience of hypnosis and variations in hypnotizability by examining research employing functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and electroencephalography (EEG) methods. Key focus areas include functional brain imaging correlations in hypnosis, EEG band [...] Read more.

This comprehensive review delves into the cognitive neuroscience of hypnosis and variations in hypnotizability by examining research employing functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and electroencephalography (EEG) methods. Key focus areas include functional brain imaging correlations in hypnosis, EEG band oscillations as indicators of hypnotic states, alterations in EEG functional connectivity during hypnosis and wakefulness, drawing critical conclusions, and suggesting future research directions. The reviewed functional connectivity findings support the notion that disruptions in the available integration between different components of the executive control network during hypnosis may correspond to altered subjective appraisals of the agency during the hypnotic response, as per dissociated and cold control theories of hypnosis. A promising exploration avenue involves investigating how frontal lobes’ neurochemical and aperiodic components of the EEG activity at waking-rest are linked to individual differences in hypnotizability. Future studies investigating the effects of hypnosis on brain function should prioritize examining distinctive activation patterns across various neural networks. Full article

(This article belongs to the Special Issue Brain Mechanism of Hypnosis)

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21 pages, 1844 KiB

Open AccessEditor’s ChoiceReview

Rett Syndrome and the Role of MECP2: Signaling to Clinical Trials

by Adele Gaspar Lopes, Sampath Kumar Loganathan and Jayalakshmi Caliaperumal

Brain Sci. 2024, 14(2), 120; https://doi.org/10.3390/brainsci14020120 - 24 Jan 2024

Cited by 4 | Viewed by 4813

Abstract

Rett syndrome (RTT) is a neurological disorder that mostly affects females, with a frequency of 1 in 10,000 to 20,000 live birth cases. Symptoms include stereotyped hand movements; impaired learning, language, and communication skills; sudden loss of speech; reduced lifespan; retarded growth; disturbance [...] Read more.

Rett syndrome (RTT) is a neurological disorder that mostly affects females, with a frequency of 1 in 10,000 to 20,000 live birth cases. Symptoms include stereotyped hand movements; impaired learning, language, and communication skills; sudden loss of speech; reduced lifespan; retarded growth; disturbance of sleep and breathing; seizures; autism; and gait apraxia. Pneumonia is the most common cause of death for patients with Rett syndrome, with a survival rate of 77.8% at 25 years of age. Survival into the fifth decade is typical in Rett syndrome, and the leading cause of death is cardiorespiratory compromise. Rett syndrome progression has multiple stages; however, most phenotypes are associated with the nervous system and brain. In total, 95% of Rett syndrome cases are due to mutations in the MECP2 gene, an X-linked gene that encodes for the methyl CpG binding protein, a regulator of gene expression. In this review, we summarize the recent developments in the field of Rett syndrome and therapeutics targeting MECP2. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Brain Development and Psychiatric Diseases)

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21 pages, 342 KiB

Open AccessEditor’s ChoiceArticle

Associations between Gross and Fine Motor Skills, Physical Activity, Executive Function, and Academic Achievement: Longitudinal Findings from the UK Millennium Cohort Study

by Yuxi Zhou and Andrew Tolmie

Brain Sci. 2024, 14(2), 121; https://doi.org/10.3390/brainsci14020121 - 24 Jan 2024

Cited by 4 | Viewed by 6611

Abstract

Accumulating evidence from behavioral studies and neuroscience suggests that motor and cognitive development are intrinsically intertwined. To explore the underlying mechanisms of this motor–cognition link, our study examined the longitudinal relationship of early motor skills and physical activity with later cognitive skills. The [...] Read more.

Accumulating evidence from behavioral studies and neuroscience suggests that motor and cognitive development are intrinsically intertwined. To explore the underlying mechanisms of this motor–cognition link, our study examined the longitudinal relationship of early motor skills and physical activity with later cognitive skills. The sample was 3188 children from the United Kingdom Millennium Cohort Study, followed at 9 months and 5, 7, and 11 years. Early motor skills were examined at 9 months. Children’s daily physical activity level was measured using accelerometers at 7 years and a questionnaire was conducted at 11 years. Cognitive skills, including executive function and academic achievement, were measured at age 11. The results suggest that gross motor skills were positively associated with spatial working memory, whereas fine motor skills were predictive of good English and science outcomes. Moderate-to-vigorous activity was found to be negatively associated with English performance, although self-reported activity frequency was positively linked to math. Our results highlight the significant role of both gross and fine motor skills in cognitive development. This study also elucidates the limitations of using activity intensity to assess the impact of motor activity on children’s cognitive development, suggesting that attention to the effects of specific types of physical activity would better elucidate the motor/cognition link. Full article

(This article belongs to the Special Issue Executive Functioning Development—Measurements and Promotion in Naturalistic Setups)

15 pages, 441 KiB

Open AccessEditor’s ChoiceArticle

Crime Risk and Depression Differentially Relate to Aspects of Sleep in Patients with Major Depression or Social Anxiety

by Heide Klumpp, Cope Feurer, Fini Chang and Mary C. Kapella

Brain Sci. 2024, 14(1), 104; https://doi.org/10.3390/brainsci14010104 - 22 Jan 2024

Viewed by 3139

Abstract

Individuals with internalizing conditions such as depression or anxiety are at risk of sleep difficulties. Social–ecological models of sleep health propose factors at the individual (e.g., mental health) and neighborhood (e.g., crime risk) levels that contribute to sleep difficulties. However, these relationships have [...] Read more.

Individuals with internalizing conditions such as depression or anxiety are at risk of sleep difficulties. Social–ecological models of sleep health propose factors at the individual (e.g., mental health) and neighborhood (e.g., crime risk) levels that contribute to sleep difficulties. However, these relationships have been under-researched in terms of internalizing conditions. Therefore, the current study comprised participants diagnosed with major depression (n = 24) or social anxiety (n = 35). Sleep measures included actigraphic variables (i.e., total sleep time, waking after sleep onset, sleep onset latency) and subjective sleep quality. Geocoding was used to assess nationally-normed crime risk exposure at the person level (e.g., murder, assault) and property level (e.g., robbery, burglary). Analyses consisted of independent t-tests to evaluate potential differences between diagnostic groups. To examine relationships, multiple regressions were used with internalizing symptoms, crime risk, and age as independent variables and sleep measures as the dependent variable. The t-test results revealed that groups differed in symptoms and age but not sleep or neighborhood crime. Regression results revealed crime risk positively corresponded with sleep onset latency but no other sleep measures. Also, only depression positively corresponded with total sleep time. Preliminary findings suggest exposure to crime and depression relate differentially to facets of sleep in individuals with internalizing conditions. Full article

(This article belongs to the Section Psychiatric Diseases)

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17 pages, 323 KiB

Open AccessEditor’s ChoiceReview

The Story behind the Mask: A Narrative Review on Hypomimia in Parkinson’s Disease

by Edoardo Bianchini, Domiziana Rinaldi, Marika Alborghetti, Marta Simonelli, Flavia D’Audino, Camilla Onelli, Elena Pegolo and Francesco E. Pontieri

Brain Sci. 2024, 14(1), 109; https://doi.org/10.3390/brainsci14010109 - 22 Jan 2024

Cited by 2 | Viewed by 2853

Abstract

Facial movements are crucial for social and emotional interaction and well-being. Reduced facial expressions (i.e., hypomimia) is a common feature in patients with Parkinson’s disease (PD) and previous studies linked this manifestation to both motor symptoms of the disease and altered emotion recognition [...] Read more.

Facial movements are crucial for social and emotional interaction and well-being. Reduced facial expressions (i.e., hypomimia) is a common feature in patients with Parkinson’s disease (PD) and previous studies linked this manifestation to both motor symptoms of the disease and altered emotion recognition and processing. Nevertheless, research on facial motor impairment in PD has been rather scarce and only a limited number of clinical evaluation tools are available, often suffering from poor validation processes and high inter- and intra-rater variability. In recent years, the availability of technology-enhanced quantification methods of facial movements, such as automated video analysis and machine learning application, led to increasing interest in studying hypomimia in PD. In this narrative review, we summarize the current knowledge on pathophysiological hypotheses at the basis of hypomimia in PD, with particular focus on the association between reduced facial expressions and emotional processing and analyze the current evaluation tools and management strategies for this symptom, as well as future research perspectives. Full article

(This article belongs to the Collection Hot Topics in Parkinson’s Disease: State of the Art and Future Perspectives)

32 pages, 498 KiB

Open AccessEditor’s ChoiceReview

Rethinking Clozapine: Lights and Shadows of a Revolutionary Drug

by Liliana Dell’Osso, Chiara Bonelli, Benedetta Nardi, Federico Giovannoni, Cristiana Pronestì, Ivan Mirko Cremone, Giulia Amatori, Stefano Pini and Barbara Carpita

Brain Sci. 2024, 14(1), 103; https://doi.org/10.3390/brainsci14010103 - 20 Jan 2024

Cited by 4 | Viewed by 4447

Abstract

The current literature globally highlights the efficacy of Clozapine in several psychiatric disorders all over the world, with an FDA indication for reducing the risk of repeated suicidal behavior in patients with schizophrenia or schizoaffective disorder. A growing field of research is also [...] Read more.

The current literature globally highlights the efficacy of Clozapine in several psychiatric disorders all over the world, with an FDA indication for reducing the risk of repeated suicidal behavior in patients with schizophrenia or schizoaffective disorder. A growing field of research is also stressing a possible broader beneficial effect of Clozapine in promoting neuroprotection and neurotrophism. However, this drug is linked to several life-threatening side effects, such as agranulocytosis, myocarditis and seizures, that limit its use in daily clinical practice. For this work, a search was performed on PubMed using the terms “Clozapine indications”, “Clozapine adverse effects”, “Clozapine regenerative effects”, and “Clozapine neuroplasticity” with the aim of reviewing the scientific literature on Clozapine’s treatment indications, adverse effects and potential regenerative role. The results confirmed the efficacy of clozapine in clinical practice, although limited by its adverse effects. It appears crucial to raise awareness among clinicians about the potential benefits of using Clozapine, as well educating medical personnel about its risks and the early identification of possible adverse effects and their management. Full article

(This article belongs to the Section Psychiatric Diseases)

15 pages, 318 KiB

Open AccessEditor’s ChoiceReview

Single-Sided Deafness and Hearing Rehabilitation Modalities: Contralateral Routing of Signal Devices, Bone Conduction Devices, and Cochlear Implants

by Alessandra Pantaleo, Alessandra Murri, Giada Cavallaro, Vito Pontillo, Debora Auricchio and Nicola Quaranta

Brain Sci. 2024, 14(1), 99; https://doi.org/10.3390/brainsci14010099 - 20 Jan 2024

Cited by 2 | Viewed by 3661

Abstract

Single sided deafness (SSD) is characterized by significant sensorineural hearing loss, severe or profound, in only one ear. SSD adversely affects various aspects of auditory perception, including causing impairment in sound localization, difficulties with speech comprehension in noisy environments, and decreased spatial awareness, [...] Read more.

Single sided deafness (SSD) is characterized by significant sensorineural hearing loss, severe or profound, in only one ear. SSD adversely affects various aspects of auditory perception, including causing impairment in sound localization, difficulties with speech comprehension in noisy environments, and decreased spatial awareness, resulting in a significant decline in overall quality of life (QoL). Several treatment options are available for SSD, including cochlear implants (CI), contralateral routing of signal (CROS), and bone conduction devices (BCD). The lack of consensus on outcome domains and measurement tools complicates treatment comparisons and decision-making. This narrative overview aims to summarize the treatment options available for SSD in adult and pediatric populations, discussing their respective advantages and disadvantages. Rerouting devices (CROS and BCD) attenuate the effects of head shadow and improve sound awareness and signal-to-noise ratio in the affected ear; however, they cannot restore binaural hearing. CROS devices, being non-implantable, are the least invasive option. Cochlear implantation is the only strategy that can restore binaural hearing, delivering significant improvements in speech perception, spatial localization, tinnitus control, and overall QoL. Comprehensive preoperative counseling, including a discussion of alternative technologies, implications of no treatment, expectations, and auditory training, is critical to optimizing therapeutic outcomes. Full article

(This article belongs to the Special Issue Middle Ear and Bone Conduction Implants)

14 pages, 823 KiB

Open AccessEditor’s ChoiceSystematic Review

Dual-Process Theory of Thought and Inhibitory Control: An ALE Meta-Analysis

by Giorgio Gronchi, Gioele Gavazzi, Maria Pia Viggiano and Fabio Giovannelli

Brain Sci. 2024, 14(1), 101; https://doi.org/10.3390/brainsci14010101 - 20 Jan 2024

Cited by 1 | Viewed by 4243

Abstract

The dual-process theory of thought rests on the co-existence of two different thinking modalities: a quick, automatic, and associative process opposed to a slow, thoughtful, and deliberative process. The increasing interest in determining the neural foundation of the dual-process distinction has yielded mixed [...] Read more.

The dual-process theory of thought rests on the co-existence of two different thinking modalities: a quick, automatic, and associative process opposed to a slow, thoughtful, and deliberative process. The increasing interest in determining the neural foundation of the dual-process distinction has yielded mixed results, also given the difficulty of applying the fMRI standard approach to tasks usually employed in the cognitive literature. We report an activation likelihood estimation (ALE) meta-analysis to investigate the neural foundation of the dual-process theory of thought. Eligible studies allowed for the identification of cerebral areas associated with dual-process theory-based tasks without differentiating between fast and slow thinking. The ALE algorithm converged on the medial frontal cortex, superior frontal cortex, anterior cingulate cortex, insula, and left inferior frontal gyrus. These structures partially overlap with the cerebral areas recurrently reported in the literature about the neural basis of the dual-process distinction, where the PARCS theory-based interpretation emphasizes the role of the right inferior gyrus. The results confirm the potential (but still almost unexplored) common ground between the dual-process literature and the cognitive control literature. Full article

(This article belongs to the Section Behavioral Neuroscience)

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28 pages, 1067 KiB

Open AccessEditor’s ChoiceReview

International Trends in Lithium Use for Pharmacotherapy and Clinical Correlates in Bipolar Disorder: A Scoping Review

by Yao Kang Shuy, Sanjana Santharan, Qian Hui Chew and Kang Sim

Brain Sci. 2024, 14(1), 102; https://doi.org/10.3390/brainsci14010102 - 20 Jan 2024

Cited by 3 | Viewed by 2308

Abstract

Lithium remains an effective option in the treatment of bipolar disorder (BD). Thus, we aim to characterize the pharmaco-epidemiological patterns of lithium use internationally over time and elucidate clinical correlates associated with BD using a scoping review, which was conducted using the methodological [...] Read more.

Lithium remains an effective option in the treatment of bipolar disorder (BD). Thus, we aim to characterize the pharmaco-epidemiological patterns of lithium use internationally over time and elucidate clinical correlates associated with BD using a scoping review, which was conducted using the methodological framework by Arksey and O’Malley (2005). We searched several databases for studies that examined the prescriptions for lithium and clinical associations in BD from inception until December 2023. This review included 55 articles from 1967 to 2023, which collected data from North America (n = 24, 43.6%), Europe (n = 20, 36.4%), and Asia (n = 11, 20.0%). The overall prescription rates ranged from 3.3% to 84% (33.4% before and 30.6% after the median year cutoffs). Over time, there was a decline in lithium use in North America (27.7% before 2010 to 17.1% after 2010) and Europe (36.7% before 2003 to 35.7% after 2003), and a mild increase in Asia (25.0% before 2003 to 26.2% after 2003). Lithium use was associated with specific demographic (e.g., age, male gender) and clinical factors (e.g., lower suicide risk). Overall, we found a trend of declining lithium use internationally, particularly in the West. Specific clinical correlates can support clinical decision-making for continued lithium use. Full article

(This article belongs to the Special Issue Neuropsychopharmacology in Mood Disorders)

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32 pages, 2585 KiB

Open AccessEditor’s ChoiceReview

Epigallocatechin-3-Gallate and Genistein for Decreasing Gut Dysbiosis, Inhibiting Inflammasomes, and Aiding Autophagy in Alzheimer’s Disease

by Ahalya Muraleedharan and Swapan K. Ray

Brain Sci. 2024, 14(1), 96; https://doi.org/10.3390/brainsci14010096 - 19 Jan 2024

Cited by 1 | Viewed by 2691

Abstract

There are approximately 24 million cases of Alzheimer’s disease (AD) worldwide, and the number of cases is expected to increase four-fold by 2050. AD is a neurodegenerative disease that leads to severe dementia in most patients. There are several neuropathological signs of AD, [...] Read more.

There are approximately 24 million cases of Alzheimer’s disease (AD) worldwide, and the number of cases is expected to increase four-fold by 2050. AD is a neurodegenerative disease that leads to severe dementia in most patients. There are several neuropathological signs of AD, such as deposition of amyloid beta (Aβ) plaques, formation of neurofibrillary tangles (NFTs), neuronal loss, activation of inflammasomes, and declining autophagy. Several of these hallmarks are linked to the gut microbiome. The gastrointestinal (GI) tract contains microbial diversity, which is important in regulating several functions in the brain via the gut-brain axis (GBA). The disruption of the balance in the gut microbiota is known as gut dysbiosis. Recent studies strongly support that targeting gut dysbiosis with selective bioflavonoids is a highly plausible solution to attenuate activation of inflammasomes (contributing to neuroinflammation) and resume autophagy (a cellular mechanism for lysosomal degradation of the damaged components and recycling of building blocks) to stop AD pathogenesis. This review is focused on two bioflavonoids, specifically epigallocatechin-3-gallate (EGCG) and genistein (GS), as a possible new paradigm of treatment for maintaining healthy gut microbiota in AD due to their implications in modulating crucial AD signaling pathways. The combination of EGCG and GS has a higher potential than either agent alone to attenuate the signaling pathways implicated in AD pathogenesis. The effects of EGCG and GS on altering gut microbiota and GBA were also explored, along with conclusions from various delivery methods to increase the bioavailability of these bioflavonoids in the body. Full article

(This article belongs to the Topic Applications of Biomedical Technology and Molecular Biological Approach in Brain Diseases)

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15 pages, 5109 KiB

Open AccessEditor’s ChoiceReview

The Role of Calcium and Iron Homeostasis in Parkinson’s Disease

by Ji Wang, Jindong Zhao, Kunying Zhao, Shangpeng Wu, Xinglong Chen and Weiyan Hu

Brain Sci. 2024, 14(1), 88; https://doi.org/10.3390/brainsci14010088 - 17 Jan 2024

Cited by 3 | Viewed by 3220

Abstract

Calcium and iron are essential elements that regulate many important processes of eukaryotic cells. Failure to maintain homeostasis of calcium and iron causes cell dysfunction or even death. PD (Parkinson’s disease) is the second most common neurological disorder in humans, for which there [...] Read more.

Calcium and iron are essential elements that regulate many important processes of eukaryotic cells. Failure to maintain homeostasis of calcium and iron causes cell dysfunction or even death. PD (Parkinson’s disease) is the second most common neurological disorder in humans, for which there are currently no viable treatment options or effective strategies to cure and delay progression. Pathological hallmarks of PD, such as dopaminergic neuronal death and intracellular α-synuclein deposition, are closely involved in perturbations of iron and calcium homeostasis and accumulation. Here, we summarize the mechanisms by which Ca²⁺ signaling influences or promotes PD progression and the main mechanisms involved in ferroptosis in Parkinson’s disease. Understanding the mechanisms by which calcium and iron imbalances contribute to the progression of this disease is critical to developing effective treatments to combat this devastating neurological disorder. Full article

(This article belongs to the Special Issue Molecular Mechanism and Pathology of Parkinson's Disease)

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13 pages, 2296 KiB

Open AccessEditor’s ChoiceReview

Update on How to Approach a Patient with Locked-In Syndrome and Their Communication Ability

by Kaitlyn Voity, Tara Lopez, Jessie P. Chan and Brian D. Greenwald

Brain Sci. 2024, 14(1), 92; https://doi.org/10.3390/brainsci14010092 - 17 Jan 2024

Cited by 2 | Viewed by 3391

Abstract

Locked-in syndrome (LIS) is a rare and challenging condition that results in tetraplegia and cranial nerve paralysis while maintaining consciousness and variable cognitive function. Once acute management is completed, it is important to work with the patient on developing a plan to maintain [...] Read more.

Locked-in syndrome (LIS) is a rare and challenging condition that results in tetraplegia and cranial nerve paralysis while maintaining consciousness and variable cognitive function. Once acute management is completed, it is important to work with the patient on developing a plan to maintain and improve their quality of life (QOL). A key component towards increasing or maintaining QOL within this population involves the establishment of a functional communication system. Evaluating cognition in patients with LIS is vital for evaluating patients’ communication needs along with physical rehabilitation to maximize their QOL. In the past decade or so, there has been an increase in research surrounding brain–computer interfaces to improve communication abilities for paralyzed patients. This article provides an update on the available technology and the protocol for finding the best way for patients with this condition to communicate. This article aims to increase knowledge of how to enhance and manage communication among LIS patients. Full article

(This article belongs to the Special Issue Recent Advances in Assessment and Rehabilitation of Individuals with Communication and Language Disorders)

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15 pages, 278 KiB

Open AccessEditor’s ChoiceReview

The Clinical Relevance of Artificial Intelligence in Migraine

by Angelo Torrente, Simona Maccora, Francesco Prinzi, Paolo Alonge, Laura Pilati, Antonino Lupica, Vincenzo Di Stefano, Cecilia Camarda, Salvatore Vitabile and Filippo Brighina

Brain Sci. 2024, 14(1), 85; https://doi.org/10.3390/brainsci14010085 - 16 Jan 2024

Cited by 7 | Viewed by 2648

Abstract

Migraine is a burdensome neurological disorder that still lacks clear and easily accessible diagnostic biomarkers. Furthermore, a straightforward pathway is hard to find for migraineurs’ management, so the search for response predictors has become urgent. Nowadays, artificial intelligence (AI) has pervaded almost every [...] Read more.

Migraine is a burdensome neurological disorder that still lacks clear and easily accessible diagnostic biomarkers. Furthermore, a straightforward pathway is hard to find for migraineurs’ management, so the search for response predictors has become urgent. Nowadays, artificial intelligence (AI) has pervaded almost every aspect of our lives, and medicine has not been missed. Its applications are nearly limitless, and the ability to use machine learning approaches has given researchers a chance to give huge amounts of data new insights. When it comes to migraine, AI may play a fundamental role, helping clinicians and patients in many ways. For example, AI-based models can increase diagnostic accuracy, especially for non-headache specialists, and may help in correctly classifying the different groups of patients. Moreover, AI models analysing brain imaging studies reveal promising results in identifying disease biomarkers. Regarding migraine management, AI applications showed value in identifying outcome measures, the best treatment choices, and therapy response prediction. In the present review, the authors introduce the various and most recent clinical applications of AI regarding migraine. Full article

(This article belongs to the Special Issue Deep into the Brain: Artificial Intelligence in Brain Diseases)

30 pages, 1472 KiB

Open AccessEditor’s ChoiceReview

Pathophysiology to Risk Factor and Therapeutics to Treatment Strategies on Epilepsy

by Ana Paula de Araújo Boleti, Pedro Henrique de Oliveira Cardoso, Breno Emanuel Farias Frihling, Luiz Filipe Ramalho Nunes de Moraes, Ellynes Amancio Correia Nunes, Lincoln Takashi Hota Mukoyama, Ellydberto Amancio Correia Nunes, Cristiano Marcelo Espinola Carvalho, Maria Lígia Rodrigues Macedo and Ludovico Migliolo

Brain Sci. 2024, 14(1), 71; https://doi.org/10.3390/brainsci14010071 - 10 Jan 2024

Cited by 7 | Viewed by 5147

Abstract

Epilepsy represents a condition in which abnormal neuronal discharges or the hyperexcitability of neurons occur with synchronicity, presenting a significant public health challenge. Prognostic factors, such as etiology, electroencephalogram (EEG) abnormalities, the type and number of seizures before treatment, as well as the [...] Read more.

Epilepsy represents a condition in which abnormal neuronal discharges or the hyperexcitability of neurons occur with synchronicity, presenting a significant public health challenge. Prognostic factors, such as etiology, electroencephalogram (EEG) abnormalities, the type and number of seizures before treatment, as well as the initial unsatisfactory effects of medications, are important considerations. Although there are several third-generation antiepileptic drugs currently available, their multiple side effects can negatively affect patient quality of life. The inheritance and etiology of epilepsy are complex, involving multiple underlying genetic and epigenetic mechanisms. Different neurotransmitters play crucial roles in maintaining the normal physiology of different neurons. Dysregulations in neurotransmission, due to abnormal transmitter levels or changes in their receptors, can result in seizures. In this review, we address the roles played by various neurotransmitters and their receptors in the pathophysiology of epilepsy. Furthermore, we extensively explore the neurological mechanisms involved in the development and progression of epilepsy, along with its risk factors. Furthermore, we highlight the new therapeutic targets, along with pharmacological and non-pharmacological strategies currently employed in the treatment of epileptic syndromes, including drug interventions employed in clinical trials related to epilepsy. Full article

(This article belongs to the Special Issue Recent Advances in Pathophysiology and Therapeutic Approaches in Epilepsy)

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24 pages, 3328 KiB

Open AccessEditor’s ChoiceReview

Being in Virtual Reality and Its Influence on Brain Health—An Overview of Benefits, Limitations and Prospects

by Beata Sokołowska

Brain Sci. 2024, 14(1), 72; https://doi.org/10.3390/brainsci14010072 - 10 Jan 2024

Cited by 7 | Viewed by 5289

Abstract

Background: Dynamic technological development and its enormous impact on modern societies are posing new challenges for 21st-century neuroscience. A special place is occupied by technologies based on virtual reality (VR). VR tools have already played a significant role in both basic and clinical [...] Read more.

Background: Dynamic technological development and its enormous impact on modern societies are posing new challenges for 21st-century neuroscience. A special place is occupied by technologies based on virtual reality (VR). VR tools have already played a significant role in both basic and clinical neuroscience due to their high accuracy, sensitivity and specificity and, above all, high ecological value. Objective: Being in a digital world affects the functioning of the body as a whole and its individual systems. The data obtained so far, both from experimental and modeling studies, as well as (clinical) observations, indicate their great and promising potential, but apart from the benefits, there are also losses and negative consequences for users. Methods: This review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework across electronic databases (such as Web of Science Core Collection; PubMed; and Scopus, Taylor & Francis Online and Wiley Online Library) to identify beneficial effects and applications, as well as adverse impacts, especially on brain health in human neuroscience. Results: More than half of these articles were published within the last five years and represent state-of-the-art approaches and results (e.g., 54.7% in Web of Sciences and 63.4% in PubMed), with review papers accounting for approximately 16%. The results show that in addition to proposed novel devices and systems, various methods or procedures for testing, validation and standardization are presented (about 1% of articles). Also included are virtual developers and experts, (bio)(neuro)informatics specialists, neuroscientists and medical professionals. Conclusions: VR environments allow for expanding the field of research on perception and cognitive and motor imagery, both in healthy and patient populations. In this context, research on neuroplasticity phenomena, including mirror neuron networks and the effects of applied virtual (mirror) tasks and training, is of interest in virtual prevention and neurogeriatrics, especially in neurotherapy and neurorehabilitation in basic/clinical and digital neuroscience. Full article

(This article belongs to the Special Issue Perception, Motor Imagery, and Action in Real Research and Virtual Environments)

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18 pages, 1338 KiB

Open AccessEditor’s ChoiceArticle

Autistic Traits as Predictors of Increased Obsessive–Compulsive Disorder Severity: The Role of Inflexibility and Communication Impairment

by Liliana Dell’Osso, Benedetta Nardi, Chiara Bonelli, Giulia Amatori, Maria Alessandra Pereyra, Enrico Massimetti, Ivan Mirko Cremone, Stefano Pini and Barbara Carpita

Brain Sci. 2024, 14(1), 64; https://doi.org/10.3390/brainsci14010064 - 9 Jan 2024

Cited by 2 | Viewed by 3641

Abstract

Due to similar manifestations, some authors have proposed a potential correlation between autism spectrum disorder (ASD) and obsessive–compulsive disorder (OCD). This link has long been recognized and debated, with some authors arguing that these disorders frequently occur comorbid but distinct while others believe [...] Read more.

Due to similar manifestations, some authors have proposed a potential correlation between autism spectrum disorder (ASD) and obsessive–compulsive disorder (OCD). This link has long been recognized and debated, with some authors arguing that these disorders frequently occur comorbid but distinct while others believe they are part of the same spectrum. The aim of our study was to explore the prevalence and correlates of autistic traits in 55 OCD patients and 55 matched controls and to assess possible autistic dimensions predictive of higher OCD symptoms. All participants were assessed with the Obsessive–Compulsive Spectrum-Short Version (OBS-SV) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). The OCD group scored significantly higher in both questionnaires. Total OBS-SV scores and domains were significantly correlated with all AdAS Spectrum domains and total score. The AdAS Spectrum total, Verbal Communication and Inflexibility and adherence to routine domain scores were significant positive predictors of higher OBS-SV scores. Lastly, when two clusters of subjects (high and low autism) were determined, Inflexibility and adherence to routine domain presented the greatest influence in forming the clusters. Our findings support the association between OCD and autistic traits in the adult population, supporting the hypothesis of a neurodevelopmental basis for these psychiatric conditions. Full article

(This article belongs to the Section Psychiatric Diseases)

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11 pages, 865 KiB

Open AccessEditor’s ChoiceArticle

The Association between Working Memory and Divergent Thinking: The Moderating Role of Formal Musical Background

by Maria Chiara Pino, Marco Giancola, Massimiliano Palmiero and Simonetta D’Amico

Brain Sci. 2024, 14(1), 61; https://doi.org/10.3390/brainsci14010061 - 8 Jan 2024

Viewed by 4217

Abstract

Divergent thinking (DT) is widely considered an essential cognitive dimension of creativity, which involves goal-oriented processes, including working memory (WM), which allows for retrieving and loading of information into the attentional stream and, consequently, enhancing divergence of thinking. Despite the critical role of [...] Read more.

Divergent thinking (DT) is widely considered an essential cognitive dimension of creativity, which involves goal-oriented processes, including working memory (WM), which allows for retrieving and loading of information into the attentional stream and, consequently, enhancing divergence of thinking. Despite the critical role of WM in DT, little work has been done on the mechanism affecting this interplay. The current study addressed the involvement of a formal musical background in the relationship between WM and DT and was conducted with 83 healthy young adults (M = 19.64 years; SD = 0.52 years; 33 females). The participants were requested to indicate if they had a formal background in music in the conservatory (M = 4.78 years; SD = 5.50 years) as well as perform the digit span forward test (DSFT) and the alternative uses task—AUT from the Torrance test of creative thinking (TTCT). The results indicated that years of formal musical background moderated the association between WM and DT. These findings suggest that music enhances the positive effect of high-order cognitive processes, such as WM, on the ability to think divergently. Theoretical and practical implications as well as limitations were discussed. Full article

(This article belongs to the Special Issue The Role of Sounds and Music in Emotion and Cognition)

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19 pages, 19765 KiB

Open AccessEditor’s ChoiceArticle

The Effects of Distancing Design Collaboration Necessitated by COVID-19 on Brain Synchrony in Teams Compared to Co-Located Design Collaboration: A Preliminary Study

by Yi-Teng Shih, Luqian Wang, Clive H. Y. Wong, Emily L. L. Sin, Matthias Rauterberg, Zhen Yuan and Leanne Chang

Brain Sci. 2024, 14(1), 60; https://doi.org/10.3390/brainsci14010060 - 7 Jan 2024

Viewed by 2612

Abstract

Due to the widespread involvement of distributed collaboration triggered by COVID-19, it has become a new trend that has continued into the post-pandemic era. This study investigated collective performance within two collaborative environments (co-located and distancing settings) by assessing inter-brain synchrony patterns (IBS) [...] Read more.

Due to the widespread involvement of distributed collaboration triggered by COVID-19, it has become a new trend that has continued into the post-pandemic era. This study investigated collective performance within two collaborative environments (co-located and distancing settings) by assessing inter-brain synchrony patterns (IBS) among design collaborators using functional near-infrared spectroscopy. The preliminary study was conducted with three dyads who possessed 2–3 years of professional product design experience. Each dyad completed two designated design tasks in distinct settings. In the distributed condition, participants interacted through video conferencing in which they were allowed to communicate by verbalization and sketching using a shared digital whiteboard. To prevent the influences of different sketching tools on design outputs, we employed digital sketching for both environments. The interactions between collaborators were identified in three behaviors: verbal only, sketch only, and mixed communication (verbal and sketch). The consequences revealed a higher level of IBS when mixed communication took place in distributed conditions than in co-located conditions. Comparably, the occurrence of IBS increased when participants solely utilized sketching as the interaction approach within the co-located setting. A mixed communication method combining verbalization and sketching might lead to more coordinated cognitive processes when in physical isolation. Design collaborators are inclined to adjust their interaction behaviors in order to adapt to different design environments, strengthen the exchange of ideas, and construct design consensus. Overall, the present paper discussed the performance of virtual collaborative design based on a neurocognitive perspective, contributing valuable insights for the future intervention design that promotes effective virtual teamwork. Full article

(This article belongs to the Special Issue Advances of AI in Neuroimaging)

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16 pages, 1928 KiB

Open AccessEditor’s ChoiceReview

Brain Health and Cognition in Older Adults: Roadmap and Milestones towards the Implementation of Preventive Strategies

by Federico Emanuele Pozzi, Giulia Remoli, Lucio Tremolizzo, Ildebrando Appollonio, Carlo Ferrarese and Luca Cuffaro

Brain Sci. 2024, 14(1), 55; https://doi.org/10.3390/brainsci14010055 - 6 Jan 2024

Viewed by 3890

Abstract

In this narrative review, we delve into the evolving concept of brain health, as recognized by the WHO, focusing on its intersection with cognitive decline. We emphasize the imperative need for preventive strategies, particularly in older adults. We describe the target population that [...] Read more.

In this narrative review, we delve into the evolving concept of brain health, as recognized by the WHO, focusing on its intersection with cognitive decline. We emphasize the imperative need for preventive strategies, particularly in older adults. We describe the target population that might benefit the most from risk-based approaches—namely, people with subjective cognitive decline. Additionally, we consider universal prevention in cognitively unimpaired middle-aged and older adults. Delving into multidomain personalized preventive strategies, we report on empirical evidence surrounding modifiable risk factors and interventions crucial in mitigating cognitive decline. Next, we highlight the emergence of brain health services (BHS). We explain their proposed role in risk assessment, risk communication, and tailored interventions to reduce the risk of dementia. Commenting on ongoing BHS pilot experiences, we present the inception and framework of our own BHS in Monza, Italy, outlining its operational structure and care pathways. We emphasize the need for global collaboration and intensified research efforts to address the intricate determinants of brain health and their potential impact on healthcare systems worldwide. Full article

(This article belongs to the Special Issue Advances in Research on Brain Health and Dementia: Prevention and Early Detection of Cognitive Decline and Dementia)

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14 pages, 662 KiB

Open AccessEditor’s ChoiceSystematic Review

Effects of Resistance Training on Spasticity in People with Stroke: A Systematic Review

by Juan Carlos Chacon-Barba, Jose A. Moral-Munoz, Amaranta De Miguel-Rubio and David Lucena-Anton

Brain Sci. 2024, 14(1), 57; https://doi.org/10.3390/brainsci14010057 - 6 Jan 2024

Cited by 2 | Viewed by 3897

Abstract

Resistance training induces neuromuscular adaptations and its impact on spasticity remains inadequately researched. This systematic review (PROSPERO: CRD42022322164) aimed to analyze the effects of resistance training, compared with no treatment, conventional therapy, or other therapies, in people with stroke-related spasticity. A comprehensive search [...] Read more.

Resistance training induces neuromuscular adaptations and its impact on spasticity remains inadequately researched. This systematic review (PROSPERO: CRD42022322164) aimed to analyze the effects of resistance training, compared with no treatment, conventional therapy, or other therapies, in people with stroke-related spasticity. A comprehensive search was conducted up to October 2023 in PubMed, PEDro, Cochrane, Web of Science, and Scopus databases. Selection criteria were randomized controlled trials involving participants with stroke-related spasticity intervened with resistance training. The PEDro scale was used to evaluate the methodological quality. From a total of 274 articles, 23 full-text articles were assessed for eligibility and nine articles were included in the systematic review, involving 225 participants (155 males, 70 females; mean age: 59.4 years). Benefits were found to spasticity after resistance training. Furthermore, studies measuring spasticity also reported benefits to function, strength, gait, and balance. In conclusion, resistance training was superior to, or at least equal to, conventional therapy, other therapies, or no intervention for improving spasticity, as well as function, strength, gait, and balance. However, the results should be taken with caution because of the heterogeneity of the protocols used. Further research is needed to explore the effects of resistance training programs on people with stroke. Full article

(This article belongs to the Special Issue Post-stroke Rehabilitation)

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30 pages, 1610 KiB

Open AccessEditor’s ChoiceReview

Understanding the Neurotrophic Virus Mechanisms and Their Potential Effect on Systemic Lupus Erythematosus Development

by Felipe R. Uribe, Valentina P. I. González, Alexis M. Kalergis, Jorge A. Soto and Karen Bohmwald

Brain Sci. 2024, 14(1), 59; https://doi.org/10.3390/brainsci14010059 - 6 Jan 2024

Cited by 2 | Viewed by 4589

Abstract

Central nervous system (CNS) pathologies are a public health concern, with viral infections one of their principal causes. These viruses are known as neurotropic pathogens, characterized by their ability to infiltrate the CNS and thus interact with various cell populations, inducing several diseases. [...] Read more.

Central nervous system (CNS) pathologies are a public health concern, with viral infections one of their principal causes. These viruses are known as neurotropic pathogens, characterized by their ability to infiltrate the CNS and thus interact with various cell populations, inducing several diseases. The immune response elicited by neurotropic viruses in the CNS is commanded mainly by microglia, which, together with other local cells, can secrete inflammatory cytokines to fight the infection. The most relevant neurotropic viruses are adenovirus (AdV), cytomegalovirus (CMV), enterovirus (EV), Epstein–Barr Virus (EBV), herpes simplex virus type 1 (HSV-1), and herpes simplex virus type 2 (HSV-2), lymphocytic choriomeningitis virus (LCMV), and the newly discovered SARS-CoV-2. Several studies have associated a viral infection with systemic lupus erythematosus (SLE) and neuropsychiatric lupus (NPSLE) manifestations. This article will review the knowledge about viral infections, CNS pathologies, and the immune response against them. Also, it allows us to understand the relevance of the different viral proteins in developing neuronal pathologies, SLE and NPSLE. Full article

(This article belongs to the Special Issue Immune Responses to Viruses in the Central Nervous System)

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22 pages, 1818 KiB

Open AccessEditor’s ChoiceReview

Strain in the Midbrain: Impact of Traumatic Brain Injury on the Central Serotonin System

by Christopher J. O’Connell, Ryan S. Brown, Taylor M. Peach, Owen D. Traubert, Hana C. Schwierling, Gabrielle A. Notorgiacomo and Matthew J. Robson

Brain Sci. 2024, 14(1), 51; https://doi.org/10.3390/brainsci14010051 - 5 Jan 2024

Cited by 1 | Viewed by 2729

Abstract

Traumatic brain injury (TBI) is a pervasive public health crisis that severely impacts the quality of life of affected individuals. Like peripheral forms of trauma, TBI results from extraordinarily heterogeneous environmental forces being imparted on the cranial space, resulting in heterogeneous disease pathologies. [...] Read more.

Traumatic brain injury (TBI) is a pervasive public health crisis that severely impacts the quality of life of affected individuals. Like peripheral forms of trauma, TBI results from extraordinarily heterogeneous environmental forces being imparted on the cranial space, resulting in heterogeneous disease pathologies. This has made therapies for TBI notoriously difficult to develop, and currently, there are no FDA-approved pharmacotherapies specifically for the acute or chronic treatment of TBI. TBI is associated with changes in cognition and can precipitate the onset of debilitating psychiatric disorders like major depressive disorder (MDD), generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD). Complicating these effects of TBI, FDA-approved pharmacotherapies utilized to treat these disorders often fail to reach the desired level of efficacy in the context of neurotrauma. Although a complicated association, decades of work have linked central serotonin (5-HT) neurotransmission as being involved in the etiology of a myriad of neuropsychiatric disorders, including MDD and GAD. 5-HT is a biogenic monoamine neurotransmitter that is highly conserved across scales of biology. Though the majority of 5-HT is isolated to peripheral sites such as the gastrointestinal (GI) tract, 5-HT neurotransmission within the CNS exerts exquisite control over diverse biological functions, including sleep, appetite and respiration, while simultaneously establishing normal mood, perception, and attention. Although several key studies have begun to elucidate how various forms of neurotrauma impact central 5-HT neurotransmission, a full determination of precisely how TBI disrupts the highly regulated dynamics of 5-HT neuron function and/or 5-HT neurotransmission has yet to be conceptually or experimentally resolved. The purpose of the current review is, therefore, to integrate the disparate bodies of 5-HT and TBI research and synthesize insight into how new combinatorial research regarding 5-HT neurotransmission and TBI may offer an informed perspective into the nature of TBI-induced neuropsychiatric complications. Full article

(This article belongs to the Section Neuropharmacology and Neuropathology)

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17 pages, 1302 KiB

Open AccessEditor’s ChoiceReview

Neurobiological Underpinnings of Hyperarousal in Depression: A Comprehensive Review

by Musi Xie, Ying Huang, Wendan Cai, Bingqi Zhang, Haonan Huang, Qingwei Li, Pengmin Qin and Junrong Han

Brain Sci. 2024, 14(1), 50; https://doi.org/10.3390/brainsci14010050 - 4 Jan 2024

Cited by 3 | Viewed by 3390

Abstract

Patients with major depressive disorder (MDD) exhibit an abnormal physiological arousal pattern known as hyperarousal, which may contribute to their depressive symptoms. However, the neurobiological mechanisms linking this abnormal arousal to depressive symptoms are not yet fully understood. In this review, we summarize [...] Read more.

Patients with major depressive disorder (MDD) exhibit an abnormal physiological arousal pattern known as hyperarousal, which may contribute to their depressive symptoms. However, the neurobiological mechanisms linking this abnormal arousal to depressive symptoms are not yet fully understood. In this review, we summarize the physiological and neural features of arousal, and review the literature indicating abnormal arousal in depressed patients. Evidence suggests that a hyperarousal state in depression is characterized by abnormalities in sleep behavior, physiological (e.g., heart rate, skin conductance, pupil diameter) and electroencephalography (EEG) features, and altered activity in subcortical (e.g., hypothalamus and locus coeruleus) and cortical regions. While recent studies highlight the importance of subcortical–cortical interactions in arousal, few have explored the relationship between subcortical–cortical interactions and hyperarousal in depressed patients. This gap limits our understanding of the neural mechanism through which hyperarousal affects depressive symptoms, which involves various cognitive processes and the cerebral cortex. Based on the current literature, we propose that the hyperconnectivity in the thalamocortical circuit may contribute to both the hyperarousal pattern and depressive symptoms. Future research should investigate the relationship between thalamocortical connections and abnormal arousal in depression, and explore its implications for non-invasive treatments for depression. Full article

(This article belongs to the Section Psychiatric Diseases)

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41 pages, 2259 KiB

Open AccessEditor’s ChoiceSystematic Review

Molecular Targeted Therapies in Glioblastoma Multiforme: A Systematic Overview of Global Trends and Findings

by Emir Begagić, Ragib Pugonja, Hakija Bečulić, Amila Čeliković, Lejla Tandir Lihić, Samra Kadić Vukas, Lejla Čejvan, Rasim Skomorac, Edin Selimović, Belma Jaganjac, Fatima Juković-Bihorac, Aldin Jusić and Mirza Pojskić

Brain Sci. 2023, 13(11), 1602; https://doi.org/10.3390/brainsci13111602 - 17 Nov 2023

Cited by 14 | Viewed by 3488

Abstract

This systematic review assesses current molecular targeted therapies for glioblastoma multiforme (GBM), a challenging condition with limited treatment options. Using PRISMA methodology, 166 eligible studies, involving 2526 patients (61.49% male, 38.51% female, with a male-to-female ratio of 1.59/1), were analyzed. In laboratory studies, [...] Read more.

This systematic review assesses current molecular targeted therapies for glioblastoma multiforme (GBM), a challenging condition with limited treatment options. Using PRISMA methodology, 166 eligible studies, involving 2526 patients (61.49% male, 38.51% female, with a male-to-female ratio of 1.59/1), were analyzed. In laboratory studies, 52.52% primarily used human glioblastoma cell cultures (HCC), and 43.17% employed animal samples (mainly mice). Clinical participants ranged from 18 to 100 years, with 60.2% using combined therapies and 39.8% monotherapies. Mechanistic categories included Protein Kinase Phosphorylation (41.6%), Cell Cycle-Related Mechanisms (18.1%), Microenvironmental Targets (19.9%), Immunological Targets (4.2%), and Other Mechanisms (16.3%). Key molecular targets included Epidermal Growth Factor Receptor (EGFR) (10.8%), Mammalian Target of Rapamycin (mTOR) (7.2%), Vascular Endothelial Growth Factor (VEGF) (6.6%), and Mitogen-Activated Protein Kinase (MEK) (5.4%). This review provides a comprehensive assessment of molecular therapies for GBM, highlighting their varied efficacy in clinical and laboratory settings, ultimately impacting overall and progression-free survival in GBM management. Full article

(This article belongs to the Special Issue Identification of Molecular Targets and Anti-cancer Agents in Glioblastoma Multiforme: New Perspectives for Cancer Therapy)

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30 pages, 451 KiB

Open AccessEditor’s ChoiceReview

Advances in Glioblastoma Therapy: An Update on Current Approaches

by Ramcharan Singh Angom, Naga Malleswara Rao Nakka and Santanu Bhattacharya

Brain Sci. 2023, 13(11), 1536; https://doi.org/10.3390/brainsci13111536 - 31 Oct 2023

Cited by 32 | Viewed by 7155

Abstract

Glioblastoma multiforme (GBM) is a primary malignant brain tumor characterized by a high grade of malignancy and an extremely unfavorable prognosis. The current efficacy of established treatments for GBM is insufficient, necessitating the prompt development of novel therapeutic approaches. The progress made in [...] Read more.

Glioblastoma multiforme (GBM) is a primary malignant brain tumor characterized by a high grade of malignancy and an extremely unfavorable prognosis. The current efficacy of established treatments for GBM is insufficient, necessitating the prompt development of novel therapeutic approaches. The progress made in the fundamental scientific understanding of GBM is swiftly translated into more advanced stages of therapeutic studies. Despite extensive efforts to identify new therapeutic approaches, GBM exhibits a high mortality rate. The current efficacy of treatments for GBM patients is insufficient due to factors such as tumor heterogeneity, the blood–brain barrier, glioma stem cells, drug efflux pumps, and DNA damage repair mechanisms. Considering this, pharmacological cocktail therapy has demonstrated a growing efficacy in addressing these challenges. Towards this, various forms of immunotherapy, including the immune checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, and vaccine therapy have emerged as potential strategies for enhancing the prognosis of GBM. Current investigations are focused on exploring combination therapies to mitigate undesirable side effects and enhance immune responses against tumors. Furthermore, clinical trials are underway to evaluate the efficacy of several strategies to circumvent the blood–brain barrier (BBB) to achieve targeted delivery in patients suffering from recurrent GBM. In this review, we have described the biological and molecular targets for GBM therapy, pharmacologic therapy status, prominent resistance mechanisms, and new treatment approaches. We also discuss these promising therapeutic approaches to assess prospective innovative therapeutic agents and evaluated the present state of preclinical and clinical studies in GBM treatment. Overall, this review attempts to provide comprehensive information on the current status of GBM therapy. Full article

(This article belongs to the Special Issue Current Updates on Theragnostic Strategies for Intervention of Brain Diseases and Pathology)

17 pages, 541 KiB

Open AccessEditor’s ChoiceArticle

GLP-1 Receptor Agonists and Related Mental Health Issues; Insights from a Range of Social Media Platforms Using a Mixed-Methods Approach

by Davide Arillotta, Giuseppe Floresta, Amira Guirguis, John Martin Corkery, Valeria Catalani, Giovanni Martinotti, Stefano L. Sensi and Fabrizio Schifano

Brain Sci. 2023, 13(11), 1503; https://doi.org/10.3390/brainsci13111503 - 24 Oct 2023

Cited by 18 | Viewed by 11938

Abstract

The emergence of glucagon-like peptide-1 receptor agonists (GLP-1 RAs; semaglutide and others) now promises effective, non-invasive treatment of obesity for individuals with and without diabetes. Social media platforms’ users started promoting semaglutide/Ozempic as a weight-loss treatment, and the associated increase in demand has [...] Read more.

The emergence of glucagon-like peptide-1 receptor agonists (GLP-1 RAs; semaglutide and others) now promises effective, non-invasive treatment of obesity for individuals with and without diabetes. Social media platforms’ users started promoting semaglutide/Ozempic as a weight-loss treatment, and the associated increase in demand has contributed to an ongoing worldwide shortage of the drug associated with levels of non-prescribed semaglutide intake. Furthermore, recent reports emphasized some GLP-1 RA-associated risks of triggering depression and suicidal thoughts. Consistent with the above, we aimed to assess the possible impact of GLP-1 RAs on mental health as being perceived and discussed in popular open platforms with the help of a mixed-methods approach. Reddit posts yielded 12,136 comments, YouTube videos 14,515, and TikTok videos 17,059, respectively. Out of these posts/entries, most represented matches related to sleep-related issues, including insomnia (n = 620 matches); anxiety (n = 353); depression (n = 204); and mental health issues in general (n = 165). After the initiation of GLP-1 RAs, losing weight was associated with either a marked improvement or, in some cases, a deterioration, in mood; increase/decrease in anxiety/insomnia; and better control of a range of addictive behaviors. The challenges of accessing these medications were a hot topic as well. To the best of our knowledge, this is the first study documenting if and how GLP-1 RAs are perceived as affecting mood, mental health, and behaviors. Establishing a clear cause-and-effect link between metabolic diseases, depression and medications is difficult because of their possible reciprocal relationship, shared underlying mechanisms and individual differences. Further research is needed to better understand the safety profile of these molecules and their putative impact on behavioral and non-behavioral addictions. Full article

(This article belongs to the Section Neuropsychology)

20 pages, 1289 KiB

Open AccessEditor’s ChoiceReview

Reelin Signaling in Neurodevelopmental Disorders and Neurodegenerative Diseases

by Aurelie Joly-Amado, Neel Kulkarni and Kevin R. Nash

Brain Sci. 2023, 13(10), 1479; https://doi.org/10.3390/brainsci13101479 - 19 Oct 2023

Cited by 11 | Viewed by 2704

Abstract

Reelin is an extracellular matrix glycoprotein involved in neuronal migration during embryonic brain development and synaptic plasticity in the adult brain. The role of Reelin in the developing central nervous system has been extensively characterized. Indeed, a loss of Reelin or a disruption [...] Read more.

Reelin is an extracellular matrix glycoprotein involved in neuronal migration during embryonic brain development and synaptic plasticity in the adult brain. The role of Reelin in the developing central nervous system has been extensively characterized. Indeed, a loss of Reelin or a disruption in its signaling cascade leads to neurodevelopmental defects and is associated with ataxia, intellectual disability, autism, and several psychiatric disorders. In the adult brain, Reelin is critically involved in neurogenesis and synaptic plasticity. Reelin’s signaling potentiates glutamatergic and GABAergic neurotransmission, induces synaptic maturation, and increases AMPA and NMDA receptor subunits’ expression and activity. As a result, there is a growing literature reporting that a loss of function and/or reduction of Reelin is implicated in numerous neurodegenerative diseases. The present review summarizes the current state of the literature regarding the implication of Reelin and Reelin-mediated signaling during aging and neurodegenerative disorders, highlighting Reelin as a possible target in the prevention or treatment of progressive neurodegeneration. Full article

(This article belongs to the Section Neurodegenerative Diseases)

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28 pages, 1535 KiB

Open AccessEditor’s ChoiceReview

Cardiac 123I-Metaiodobenzylguanidine (MIBG) Scintigraphy in Parkinson’s Disease: A Comprehensive Review

by Jamir Pitton Rissardo and Ana Letícia Fornari Caprara

Brain Sci. 2023, 13(10), 1471; https://doi.org/10.3390/brainsci13101471 - 18 Oct 2023

Cited by 8 | Viewed by 3880

Abstract

Cardiac sympathetic denervation, as documented on 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, is relatively sensitive and specific for distinguishing Parkinson’s disease (PD) from other neurodegenerative causes of parkinsonism. The present study aims to comprehensively review the literature regarding the use of cardiac MIBG in PD. [...] Read more.

Cardiac sympathetic denervation, as documented on 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, is relatively sensitive and specific for distinguishing Parkinson’s disease (PD) from other neurodegenerative causes of parkinsonism. The present study aims to comprehensively review the literature regarding the use of cardiac MIBG in PD. MIBG is an analog to norepinephrine. They share the same uptake, storage, and release mechanisms. An abnormal result in the cardiac MIBG uptake in individuals with parkinsonism can be an additional criterion for diagnosing PD. However, a normal result of cardiac MIBG in individuals with suspicious parkinsonian syndrome does not exclude the diagnosis of PD. The findings of cardiac MIBG studies contributed to elucidating the pathophysiology of PD. We investigated the sensitivity and specificity of cardiac MIBG scintigraphy in PD. A total of 54 studies with 3114 individuals diagnosed with PD were included. The data were described as means with a Hoehn and Yahr stage of 2.5 and early and delayed registration H/M ratios of 1.70 and 1.51, respectively. The mean cutoff for the early and delayed phases were 1.89 and 1.86. The sensitivity for the early and delayed phases was 0.81 and 0.83, respectively. The specificity for the early and delayed phases were 0.86 and 0.80, respectively. Full article

(This article belongs to the Section Neurodegenerative Diseases)

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19 pages, 2039 KiB

Open AccessEditor’s ChoiceSystematic Review

The Effect of Beta-Carotene on Cognitive Function: A Systematic Review

by Diana Marisol Abrego-Guandique, Maria Luisa Bonet, Maria Cristina Caroleo, Roberto Cannataro, Paola Tucci, Joan Ribot and Erika Cione

Brain Sci. 2023, 13(10), 1468; https://doi.org/10.3390/brainsci13101468 - 17 Oct 2023

Cited by 11 | Viewed by 4259

Abstract

β-carotene is a powerful antioxidant and dietary precursor of vitamin A whose role in maintaining mental health and cognitive performance, either alone or in combination with other dietary compounds, has been a topic of recent research. However, its effectiveness is still unclear. This [...] Read more.

β-carotene is a powerful antioxidant and dietary precursor of vitamin A whose role in maintaining mental health and cognitive performance, either alone or in combination with other dietary compounds, has been a topic of recent research. However, its effectiveness is still unclear. This systematic review, conducted according to the PRISMA guideline and assisted by the MySLR platform, addressed this issue. A total of 16 eligible original research articles were identified. Dietary intake or β-carotene serum levels were associated with improved measures of cognitive function in 7 out of 10 epidemiological studies included. In intervention studies, β-carotene consumption alone did not promote better cognitive function in the short term, but only in a long-term intervention with a mean duration of 18 years. However, all but one intervention study suggested the beneficial effects of β-carotene supplementation at doses ranging from 6 mg to 50 mg per day in combination with a multicomplex such as vitamin E, vitamin C, zinc, or selenium for a period of 16 weeks to 20 years. Despite the current limitations, the available evidence suggests a potential association between β-carotene dietary/supplementary intake and the maintenance of cognitive function. The β-carotene most probably does not act alone but in synergy with other micronutrients. Full article

(This article belongs to the Special Issue Nutrition in Neurodegenerative Diseases: Prevention and Treatment)

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28 pages, 648 KiB

Open AccessEditor’s ChoiceReview

An Overview of the Body Schema and Body Image: Theoretical Models, Methodological Settings and Pitfalls for Rehabilitation of Persons with Neurological Disorders

by Davide Sattin, Chiara Parma, Christian Lunetta, Aida Zulueta, Jacopo Lanzone, Luca Giani, Marta Vassallo, Mario Picozzi and Eugenio Agostino Parati

Brain Sci. 2023, 13(10), 1410; https://doi.org/10.3390/brainsci13101410 - 4 Oct 2023

Cited by 11 | Viewed by 4273

Abstract

Given the widespread debate on the definition of the terms “Body Schema” and “Body Image”, this article presents a broad overview of the studies that have investigated the nature of these types of body representations, especially focusing on the innovative information about these [...] Read more.

Given the widespread debate on the definition of the terms “Body Schema” and “Body Image”, this article presents a broad overview of the studies that have investigated the nature of these types of body representations, especially focusing on the innovative information about these two representations that could be useful for the rehabilitation of patients with different neurological disorders with motor deficits (especially those affecting the upper limbs). In particular, we analyzed (i) the different definitions and explicative models proposed, (ii) the empirical settings used to test them and (iii) the clinical and rehabilitative implications derived from the application of interventions on specific case reports. The growing number of neurological diseases with motor impairment in the general population has required the development of new rehabilitation techniques and a new phenomenological paradigm placing body schema as fundamental and intrinsic parts for action in space. In this narrative review, the focus was placed on evidence from the application of innovative rehabilitation techniques and case reports involving the upper limbs, as body parts particularly involved in finalistic voluntary actions in everyday life, discussing body representations and their functional role. Full article

(This article belongs to the Special Issue State of the Art in Disorders of Consciousness)

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